Association between Pre-operative Body Mass Index and Surgical Infection in Perihilar Cholangiocarcinoma Patients Treated with Curative Resection: A Multi-center Study.

Background: The objective of this study was to investigate the association between pre-operative body mass index (BMI) and surgical infection in perihilar cholangiocarcinoma (pCCA) patients treated with curative resection. Methods: Consecutive pCCA patients were enrolled from four tertiary hospitals between 2008 and 2022. According to pre-operative BMI, the patients were divided into three groups: low BMI (≤18.4 kg/m2), normal BMI (18.5-24.9 kg/m2), and high BMI (≥25.0 kg/m2). The incidence of surgical infection among the three groups was compared. Multivariable logistic regression models were used to determine the independent risk factors associated with surgical infection. Results: A total of 371 patients were enrolled, including 283 patients (76.3%) in the normal BMI group, 30 patients (8.1%) in the low BMI group, and 58 patients (15.6%) in the high BMI group. The incidence of surgical infection was significantly higher in the patients in the low BMI and high BMI groups than in the normal BMI group. The multivariable logistic regression model showed that low BMI and high BMI were independently associated with the occurrence of surgical infection. Conclusions: The pCCA patients with a normal BMI treated with curative resection could have a lower risk of surgical infection than pCCA patients with an abnormal BMI.

Rft1 catalyzes lipid-linked oligosaccharide translocation across the ER membrane.

The eukaryotic asparagine (N)-linked glycan is pre-assembled as a fourteen-sugar oligosaccharide on a lipid carrier in the endoplasmic reticulum (ER). Seven sugars are first added to dolichol pyrophosphate (PP-Dol) on the cytoplasmic face of the ER, generating Man5GlcNAc2-PP-Dol (M5GN2-PP-Dol). M5GN2-PP-Dol is then flipped across the bilayer into the lumen by an ER translocator. Genetic studies identified Rft1 as the M5GN2-PP-Dol flippase in vivo but are at odds with biochemical data suggesting Rft1 is dispensable for flipping in vitro. Thus, the question of whether Rft1 plays a direct or an indirect role during M5GN2-PP-Dol translocation has been controversial for over two decades. We describe a completely reconstituted in vitro assay for M5GN2-PP-Dol translocation and demonstrate that purified Rft1 catalyzes the translocation of M5GN2-PP-Dol across the lipid bilayer. These data, combined with in vitro results demonstrating substrate selectivity and rft1∆ phenotypes, confirm the molecular identity of Rft1 as the M5GN2-PP-Dol ER flippase.

CT Characteristics and Clinical Findings of Bronchopneumonia Caused by Pepper Aspiration.

Purpose: To explore the computed tomography (CT) features of bronchopneumonia caused by pepper aspiration to improve the diagnosis. Materials and Methods: 28 adult patients diagnosed with obstructive pneumonia caused by pepper aspiration from January 2016 to September 2022 were enrolled. The CT characteristics of bronchial changes and pulmonary lesions caused by pepper were analyzed and summarized. Results: Among 28 patients, the most common symptom was cough (26, 92.9%), followed by expectoration (23, 82.1%). Bronchoscopy revealed that peppers were mainly found in the bronchus of the right lower lobe (n = 18, 64.3%), followed by the bronchus of the left lower lobe (n = 5, 17.9%). In combination with bronchoscopy results, the pepper in the bronchus manifested as circular or V/U-shaped high-density, localized soft tissue, and flocculent opacification in 8 (28.6%), 16 (57.1%), and 3 (10.7%) cases on CT images, respectively. The bronchial wall around the pepper was thickened with localized occlusion (n = 19, 67.9%) and stenosis (n = 9, 32.1%). Regarding adjacent bronchi without peppers, extensive wall thickening with stenosis and/or occlusion was found in 23 (82.1%) cases. Distal pulmonary lesions frequently involved two or three segments (21, 75.0%) and mainly presented as patchy consolidation or atelectasis (24, 85.7%). Conclusion: In combination to a history of eating peppers and clinical symptoms, bronchopneumonia caused by pepper should be highly suspected if U/V-shaped and annular high-density or localized soft tissue density is detected in the bronchi of the lower lobes, accompanied by extensive bronchial wall thickening, stenosis, or occlusion, and consolidation or atelectasis in multiple distal lung segments.

Fe-doped Cu-based bimetallic metal-organic frameworks as nanoscale microwave sensitizers for enhancing microwave thermal and dynamic therapy for hepatocellular carcinoma.

Microwave ablation (MWA) is recognized as a novel treatment modality that can kill tumor cells by heating the ions and polar molecules in these cells through high-speed rotation and friction. However, the size and location of the tumor affect the effective ablation range of microwave hyperthermia, resulting in residual tumor tissue and a high recurrence rate. Due to their tunable porous structure and high specific surface area, metal-organic frameworks (MOFs) can serve as microwave sensitizers, promoting microwave energy conversion owing to ion collisions in the porous structure of the MOFs. Moreover, iron-based compounds are known to possess peroxidase-like catalytic activity. Therefore, Fe-doped Cu bimetallic MOFs (FCMs) were prepared through a hydrothermal process. These FCM nanoparticles not only increased the efficiency of microwave-thermal energy conversion as microwave sensitizers but also promoted the generation of reactive oxygen species (ROS) by consuming glutathione (GSH) and promoted the Fenton reaction to enhance microwave dynamic therapy (MDT). The in vitro and in vivo results showed that the combination of MWA and MDT treatment effectively destroyed tumor tissues via microwave irradiation without inducing significant side effects on normal tissues. This study provides a new approach for the combined application of MOFs and microwave ablation, demonstrating excellent potential for future applications.

Study on the efficacy and mechanism of treatment of manganese-containing wastewater by pulse-alternating current coagulation.

To assess the effectiveness and underlying mechanism of pulse-alternating current coagulation (PACC) for treating manganese-laden wastewater, we examined the influence of various parameters. Specifically, we investigated the impact of current density, initial pH, initial Mn2+ concentration, electrolyte concentration, and alternating current frequency on the removal efficacy. The removal mechanism was meticulously examined using an adsorption kinetics analysis, Scanning Electron Microscope (SEM), Energy Dispersive Spectroscopy (EDS), Fourier Transform Infrared Spectrum (FTIR), and X-ray Photoelectron Spectroscopy (XPS). The findings indicated that the concentration of Re(Mn2+) was 99.09% under the specified conditions: j = 2.5 A·m-2, pH0 = 7, c0(Mn2+) = 50 mg·dm-3, f = 500 Hz, c0(NaCl) = 500 mg·dm-3 and t = 40 min. When Re(Mn2+) = 98%, the energy consumption (EEC) was significantly lower for PACC at 1.23 kWh·m-3, compared to 1.52 kWh·m-3 for direct current condensation (DCC). This indicated a reduction in EEC by 19.1% when using PACC over DCC. The adsorption process of Mn2+ by the iron sol adheres to the principles of pseudo-second order kinetics. The primary component of flocs generated in the PACC process is α-FeOOH. The mechanism of Mn2+ removal in the PACC process involved the synthesis of Mn oxides, the formation of metal hydroxide precipitates and adsorption by nano-iron sol. This study provides a theoretical basis and technical support for the application of PACC technology in the field of manganese-containing wastewater treatment.

Long-term prognosis of patients with gallbladder carcinoma after curative-intent resection based on changes in the ratio of carbohydrate antigen 19-9 to total bilirubin (CA19-9/TB): a multicenter retrospective cohort study.

BACKGROUND: The prognostic value of carbohydrate antigen 19-9 (CA19-9) is known to be affected by elevated bilirubin levels in patients with gallbladder carcinoma (GBC). The clinical significance of changes in the ratio of CA19-9 levels to total bilirubin (TB) levels in patients with GBC after curative-intent resection remains unknown. The aim of this study was to determine the prognostic value of changes in preoperative and postoperative CA19-9/TB ratio in these patients. METHODS: Prospectively collected data on consecutive patients who underwent curative-intent resection for GBC between January 2015 and December 2020 stored in a multicenter database from 10 hospitals were analyzed in this retrospective cohort study. Based on the adjusted CA19-9 defined as the ratio of CA19-9 to TB, and using 2×10 3  U/µmol as the upper normal value, patients were divided into a normal group (with normal preoperative and postoperative adjusted CA19-9), a normalization group (with abnormal preoperative but normal postoperative adjusted CA19-9), and a non-normalization group (with abnormal postoperative adjusted CA19-9). The primary outcomes were overall survival (OS) and recurrence-free survival (RFS). The log-rank test was used to compare OS and RFS among the groups. The Cox regression model was used to determine factors independently associated with OS and RFS. RESULTS: The normal group ( n =179 patients) and the normalization group ( n =73 patients) had better OS and RFS than the non-normalization group ( n =65 patients) (the 3-year OS rates 72.0%, 58.4% and 24.2%, respectively; the RFS rates 54.5%, 25.5% and 11.8%, respectively; both P <0.001). There were no significant differences between the normal and the normalization groups in OS and RFS (OS, P =0.255; RFS, P =0.130). Cox regression analysis confirmed that the non-normalization group was independently associated with worse OS and RFS. Subgroup analysis revealed that the non-normalization group of patients who received adjuvant therapy had significantly improved OS and RFS as compared to those who did not receive adjuvant therapy (OS, P =0.025; RFS, P =0.003). CONCLUSIONS: Patients with GBC who underwent curative-intent surgical resection with postoperative abnormal levels of adjusted CA19-9 (the CA19-9/TB ratio) were associated with poorer long-term survival outcomes. Adjuvant therapy after surgery improved the long-term outcomes of these patients.

Double lung transplantation is better than single lung transplantation for end-stage chronic obstructive pulmonary disease: a meta-analysis.

BACKGROUND: Lung transplantation is one of the most common treatment options for patients with end-stage chronic obstructive pulmonary disease. However, the choice between single and double lung transplantation for these patients remains a matter of debate. Therefore, we performed a systematic search of medical databases for studies on single lung transplantation, double lung transplantation, and chronic obstructive pulmonary disease. METHODS: The rate ratio and hazard ratio of survival were analyzed. The meta-analysis included 15 case-control and retrospective registry studies. RESULTS: The rate ratios of the 3-year survival (0.937 and P = 0.041) and 5-year survival (0.775 and P = 0.000) were lower for single lung transplantation than for double lung transplantation. However, the hazard ratio did not differ significantly between the two. CONCLUSIONS: Double lung transplantation was found to provide better benefits than single lung transplantation in terms of the long-term survival in patients with chronic obstructive pulmonary disease.

Production of CA125 with Tn antigens using a glycosylphosphatidylinositol anchoring system.

Cancer antigen 125 (CA125) is a serum marker associated with ovarian cancer. Despite its widespread use, CA125 levels can also be elevated in benign conditions. Recent reports suggest that detecting serum CA125 that carries the Tn antigen, a truncated O-glycan containing only N-acetylgalactosamine on serine or threonine residues, can improve the specificity of ovarian cancer diagnosis. In this study, we engineered cells to express CA125 with a Tn antigen. To achieve this, we knocked out C1GALT1 and SLC35A1, genes encoding Core1 synthase and a transporter for cytidine-5'-monophospho-sialic acid respectively, in human embryonic kidney 293 (HEK293) cells. In ClGALT1-SLC35A1-knockout (KO) cells, the expression of the Tn antigen showed a significant increase, whereas the expression of the T antigen (galactose-ß1,3-N-acetylgalactosamine on serine or threonine residues) was decreased. Due to the inefficient secretion of soluble CA125, we employed a glycosylphosphatidylinositol (GPI) anchoring system. This allowed for the expression of GPI-anchored CA125 on the cell surface of ClGALT1-SLC35A1-KO cells. Cells expressing high levels of GPI-anchored CA125 were then enriched through cell sorting. By knocking out the PGAP2 gene, the GPI-anchored form of CA125 was converted to a secretory form. Through the engineering of O-glycans and the use of a GPI-anchoring system, we successfully produced CA125 with Tn antigen modification.

Association of changes in waist circumference, waist-to-height ratio and weight-adjusted-waist index with multimorbidity among older Chinese adults: results from the Chinese longitudinal healthy longevity survey (CLHLS).

BACKGROUND: The association of changes in waist circumference (WC), waist-to-height ratio (WHtR) and weight-adjusted-waist index (WWI) with subsequent risk of multimorbidity remains unclear among older Chinese adults. Therefore, we aimed to assess this association by utilizing data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). METHODS: Our study was based on the 2011/2012 wave of the CLHLS whose follow-up surveys were conducted in 2014 and 2017/2018. A total of 2900 participants aged 65 and above at baseline were enrolled. WC, WHtR, and WWI were calculated from measured height, weight, and waist circumference. Multimorbidity refers to the coexistence of two or more of 18 chronic diseases. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95%CIs) to evaluate the effect of three-year changes in WC, WHtR, and WWI on the risk of multimorbidity. RESULTS: During a mean follow-up time of 4.2 (2.0) years, 906 multimorbidity cases were identified. Compared to participants in the persistently low WC group, those in the WC gain group and the persistently high WC group had a higher multimorbidity risk with adjusted HRs (95%CI) of 1.23 (1.01-1.50) and 1.34(1.14-1.58), respectively. Participants in the WHtR gain group and the persistently high WHtR group also had higher risks of multimorbidity with HRs (95%CI) of 1.35 (1.08-1.67) and 1.27 (1.05-1.53), respectively, relative to the persistently low WHtR group. Compared to the persistently low WWI group, those in the WWI loss group had a lower risk of multimorbidity with HRs (95%CI) of 0.80 (0.66-0.98). For every standard deviation increase in WC, WHtR, and WWI over three years, the risk of multimorbidity was higher by 12% (95%CI: 1.05-1.19), 13% (95%CI: 1.06-1.20), and 12% (95%CI: 1.05-1.20), respectively. CONCLUSIONS: Associations of changes in WC, WHtR and WWI with multimorbidity are significant among older Chinese adults. The findings highlight the importance of evaluating changes in WC, WHtR, and WWI in screening and prevention of multimorbidity in older adults.

Potential contribution of the gut microbiota to the development of portal vein thrombosis in liver cirrhosis.

Background: Portal vein thrombosis (PVT) is a serious complication of liver cirrhosis (LC) and is closely related to gut homeostasis. The study aimed to investigate the composition of gut microbiota and its putative role in PVT development in LC. Methods: 33 patients with LC admitted between January 2022 and December 2022 were enrolled in this study. Based on imaging findings, they were categorized into LC without PVT (n = 21) and LC with PVT (n = 12) groups. Fecal samples were collected from each participant and underwent 16S rDNA sequencing. Results: D-Dimer and platelet elevations were the main clinical features of LC with PVT. The alpha and beta diversity of the gut microbiota in LC with PVT group was found to be significantly higher compared to the control group. The structure of the gut microbiota was significantly different between the two groups. Based on LEfSe data, the genera Akkermansia, Eubacterium hallii group, Fusicatenibacter, and Anaerostipes were enriched in the LC with PVT, while Enterococcus, Weissella, Bacteroides, and Subdoligranulum were enriched in those of the LC subjects. Changes in microbiota structure result in significant differences in gut microbiota metabolism between the two groups. Altered levels of the microbiota genera were shown to be correlated with coagulation factor parameters. In animal experiments, the addition of Bacteroides reversed the CCl4-induced PVT. Conclusion: Liver cirrhosis with PVT led to a disorder in the gut microbiota, which was characterized by an increase in pathogenic bacteria and a decrease in beneficial bacteria. Furthermore, modulating the gut microbiota, especially Bacteroides, may be a promising therapeutic approach to reduce the progression of PVT in LC.

Golgi α-mannosidases regulate cell surface N-glycan type and ectodomain shedding of the transmembrane protease corin.

Corin is a transmembrane protease that activates natriuretic peptides on the cell membrane. Reduced cell surface targeting or increased ectodomain shedding disrupts cell membrane homeostasis of corin, thereby impairing its cell surface expression and enzyme activity. N-glycans are essential in corin ectodomain shedding. Lack of N-glycans promotes corin ectodomain shedding in the juxtamembrane and frizzled-1 domains. The nascent N-glycans, transferred onto the polypeptide of corin, undergo multistep N-glycan processing in the endoplasmic reticulum and Golgi. It remains unclear how trimming by Golgi α-mannosidases, the critical N-glycan processing steps in N-glycan maturation, may regulate corin biosynthesis. In this study, we examined the effects of kifunensine and swainsonine, the inhibitors for α-mannosidases I and II, on corin expression and function. Western analysis of corin proteins in cell lysates and conditioned media from the inhibitor-treated corin-stable HEK293 cells and AC16 cells showed that both α-mannosidases I and II were required to maintain complex N-glycans on cell surface corin and protect corin from ectodomain shedding in the juxtamembrane and frizzled-1 domains. Cell viability analysis revealed that inhibition of α-mannosidase I or II sensitized cardiomyocytes to hydrogen peroxide-induced injury via regulating corin. Moreover, either one of the two coding genes was sufficient to perform Golgi α-mannosidase I trimming of N-glycans on corin. Similarly, this sufficiency was observed in Golgi α-mannosidase II-coding genes. Inhibition of ectodomain shedding restored corin zymogen activation from kifunensine- or swainsonine-induced reduction. Together, our results show the important roles of Golgi α-mannosidases in maintaining cell membrane homeostasis and biological activities of corin.

[Theory and application of pulse diagnosis at Renying and Cunkou regions].

Renying and Cunkou pulse diagnostic method is one of the important parts of the pulse diagnosis in Huangdi Neijing (Inner Canon of Yellow Emperor) and has been controversial since its proposal. This article takes WANG Shu-he's diagnostic operation as the evidence, and is in reference of the statement, "Cun region (the region ahead of Guan region of Cunkou) determines the human life, that on the left hand refers to Renying, while on the right hand is Qikou". The pulse conditions on the left and right hands represent yin and yang. If Renying pulse on the left is greater, the diseases are in yang meridians, while if Cunkou pulse on the right is bustling, the diseases are in yin meridians. By comparing the pulse condition and strength, as well as the pulse beating (rapid and urgent) between Guan region and region ahead of Guan on the same side, the conditions of three yang and three yin meridians are detected. In treatment, based on the records of Renying and Cunkou pulse diagnosis in Huangdi Neijing, the principles are proposed for reinforcing and reducing methods on hand and foot meridians of yin and yang. Five-shu points and yuan-source points are taken as the main acupoints in acupuncture treatment. During treatment, the changes in pulse conditions should be emphasized specifically and those at Renying and Cunkou regions are the criteria for judging qi arrival and qi regulation.

Leukaemic Presentation of Small-Cell Alk-Positive Anaplastic Large Cell Lymphoma in a Young Woman-Report of a Case with 9-Year Survival.

Anaplastic large cell lymphoma (ALCL) with leukaemic presentation (either ab initio or along the course of the disease) has been rarely reported. Irrespective of ALK expression in the neoplastic cells, it features a dismal prognosis. We report a rare case of leukaemic, small cell variant ALK-positive ALCL with 9-year survival in a young woman who was treated upfront with corticosteroids and standard chemotherapy, and review thoroughly the previously published cases. Such an unexpected, good outcome hints at the existence of different clinical subgroups in the leukaemic variant of ALK-positive ALCL.

Comprehensive in silico analysis of glycosylphosphatidylinositol- anchored protein (GPI-AP) related genes expression profiles in human normal and cancer tissues.

In human cells, there are more than 146 glycosylphosphatidylinositol-anchored proteins (GPI-APs), including receptors, ligands, adhesion molecules and enzymes. The proteins are associated with membrane microdomains called lipid rafts through GPI, and plays a variety of important biological functions. At present, plenty of studies have been carried out on the biosynthesis of GPI-APs. The biosynthesis of GPI-APs requires at least 20 steps, and more than 40 GPI biosynthetic genes have been identified. However, it remains unclear how expression of GPI-AP related genes is regulated in normal and cancer tissues. In this study, we utilized gene expression data from both the TCGA database and GTEx portal to analysis the gene expression involved in GPI-AP biosynthesis and encoding GPI-APs in normal and cancer tissues. In order to perform a comprehensive analysis, we employed the GlycoMaple, a tool that is specifically designed to analyze glycosylation pathways. The results showed that compared with normal tissues, the expression of genes involved in GPI-AP biosynthesis in cancer tissues such as early glioma, glioblastoma multiforme, pancreatic cancer, testicular germ cell carcinoma, skin primary cutaneous melanoma and skin metastatic cutaneous melanoma, was changed significantly. Particularly, the expression of PIGY in these six cancers was increased. In addition, the expression of CD14, a GPI-AP gene, was increased in these six cancers. The expression of GAS1, GPC2 and GPC4 was increased only in early glioma and glioblastoma multiforme indicating that some GPI-APs such as GAS1 can be used as biomarkers of glioma. This study provides new insights into the expression of GPI-AP related genes in normal and cancer tissues, and lays a solid foundation for the development of GPI-APs as biomarkers.

Comparison of gastrointestinal ultrasound with capsule endoscopy in patients with small bowel Crohn's disease.

OBJECTIVE: We aimed to investigate the association between gastrointestinal ultrasound (GIUS) and capsule endoscopy (CE) in assessing disease activity in patients with small bowel Crohn's disease (CD). METHODS: Medical records of 74 patients with small bowel CD who were treated at our hospital between January 2020 and March 2022 were retrospectively reviewed, including 50 men and 24 women. All patients underwent both GIUS and CE within one week after their admissions. The Simple Ultrasound Scoring of Crohn's Disease (SUS-CD) and Lewis score were used to assess disease activity during GIUS and CE, respectively. P < 0.05 was considered as statistically significant. RESULTS: The area under the receiver operating characteristic curve (AUROC) of SUS-CD was 0.90 (95% confidence interval [CI] 0.81-0.99; P < 0.001). And the diagnostic accuracy of GIUS was 79.7%, with a sensitivity of 93.6%, a specificity of 81.8%, a positive predictive value of 96.7%, a negative predictive value of 69.2% in predicting active small bowel CD. Furthermore, the agreement between GIUS and CE was assessed using Spearman's correlation analysis and SUS-CD was correlated with Lewis score (r = 0.82, P < 0.001) CONCLUSION: Our findings demonstrate a strong correlation between GIUS and CE in assessing the disease activity in patients with CD affecting the small intestine.

Optical near fields for ablation of periodic structures.

The formation mechanism of laser-induced periodic surface structures (LIPSS) has been a key to high-resolution sub-diffraction lithography or high-efficiency large-area nanotexturing. We show the evolution of LIPSS formation from a nanohole seed structure to high-spatial-frequency LIPSS by using a tightly focused and rectangular-shaped laser beam with different shape-polarization orientations. Formation of LIPSS based on light intensity distribution without invoking any long-range electromagnetic modes achieved quantitative match between modeling and experiment. Our results clearly show the entire step-like and deterministic process of LIPSS evolution based on experimental data and numerical simulations, revealing the dominant structural near-field enhancement on the ripple formation. A rectangular-shaped beam with an aspect ratio of 7:3 was used to break the symmetry of a circularly shaped focus. By azimuthally rotating the orientation of the focal spot and the polarization, it is possible to visualize the far-field effect for the initial seed structure formation and the competition between the far and near fields in the subsequent structure evolution.

A lipid scramblase TMEM41B is involved in the processing and transport of GPI-anchored proteins.

Protein modification by glycosylphosphatidylinositol (GPI) takes place in the endoplasmic reticulum (ER). GPI-anchored proteins (GPI-APs) formed in the ER are transported to the cell surface through the Golgi apparatus. During transport, the GPI-anchor structure is processed. In most cells, an acyl chain modified to the inositol of GPI is removed by a GPI-inositol deacylase, PGAP1, in the ER. Inositol-deacylated GPI-APs become sensitive to bacterial phosphatidylinositol-specific phospholipase C (PI-PLC). We previously reported that GPI-APs are partially resistant to PI-PLC when PGAP1 activity is weakened by the deletion of selenoprotein T (SELT) or cleft lip and palate transmembrane protein 1 (CLPTM1). In this study, we found that the loss of TMEM41B, an ER-localized lipid scramblase, restored PI-PLC sensitivity of GPI-APs in SELT-knockout (KO) and CLPTM1-KO cells. In TMEM41B-KO cells, the transport of GPI-APs as well as transmembrane proteins from the ER to the Golgi was delayed. Furthermore, the turnover of PGAP1, which is mediated by ER-associated degradation, was slowed in TMEM41B-KO cells. Taken together, these findings indicate that inhibition of TMEM41B-dependent lipid scrambling promotes GPI-AP processing in the ER through PGAP1 stabilization and slowed protein trafficking.